In the field of blood transfusion, in addition to whole blood transfusion using a whole blood preparation prepared by adding an anti-coagulating agent to blood collected from a donor, blood component transfusion infusing only blood components necessary for the blood recipient separated from a whole blood preparation has been commonly practiced. The blood component transfusion is classified into erythrocyte transfusion, platelet transfusion, plasma transfusion, and the like according to the blood component required by the blood recipient. As the blood component preparation used for blood component transfusion, an erythrocyte preparation, a platelet preparation, a blood plasma preparation, and the like can be given.
In recent years, leukocyte-free blood transfusion in which leukocytes contained in a blood preparation are removed in advance is applied to the whole blood transfusion and blood component transfusion. This is because of a recent discovery that the leukocytes in the preparations induce side effects of blood transfusion such as headache, nausea, chills, anhemolytic exothermic reaction, alloantigen sensitization, GVHD, and virus infection. Therefore, it is necessary to reduce leukocytes in the blood preparation to a level low enough to prevent these side effects.
On the other hand, an erythrocyte preparation may include platelets that partly migrate during a centrifuge operation. Since an anhemolytic side effect that is suspected to have been caused by platelets has been reported, it is desirable to reduce platelets to a level as low as possible. Furthermore, since prion has recently been reported to be present in platelets, reduction of platelets not only from an erythrocyte preparation but also from a whole blood preparation is regarded to be highly necessary from the viewpoint of reducing a risk of prion infection. Therefore, providing a method for reducing platelets from a blood preparation at a high rate is an urgent issue.
As the method for reducing leukocytes from a cell suspension containing leukocytes, a centrifuge method of reducing leukocytes by centrifuge of the cell suspension, a filter method of filtering the cell suspension through a filter to cause leukocytes to be adsorbed in the filter, a dextran method of adding a physiological saline solution containing dextran to the cell suspension in a blood bag and, after mixing, eliminating a floating leukocyte layer by suction, and the like can be given. Of these, the filter method is widely accepted due to the advantages such as excellent leukocyte reducing capability, simple operation, and a low cost.
JP 03-158168 A describes that the concentration of leukocytes having passed through a fiber laminate exponentially decreases to the thickness of the fiber laminate. This suggests that, when a cell suspension flows in the thickness direction of the fiber laminate, leukocytes are adsorbed at a certain probability every time the leukocytes contact capturing site such as crossing points of the fibers, supporting the above-described adsorption-elimination theory.
For this reason, investigation for promoting performance of leukocyte reducing filters has conventionally been focused on increasing frequency of contact between leukocytes and fibers, specifically, on decreasing the average diameter of fibers, increasing the filling density, or using nonwoven fabrics with a uniform fiber diameter distribution (JP 02-203909 A). Quite a few prior art documents have paid attention to chemical properties on the surface of nonwoven fabrics.
Although excellent leukocyte reducing filters and platelet reducing filters can be obtained by decreasing the average diameter of fibers, increasing the filling density, or using nonwoven fabrics with a uniform fiber diameter distribution, these countermeasures tend to induce bias blood flow, resulting in ineffective performance of the entire filter and fluctuation of leukocyte reduction and platelet reduction. Therefore, improvement of chemical properties on the surface of nonwoven fabrics has been necessary.
Surface modification of nonwoven fabrics by radiation grafting is one of a few studies dealing with chemical properties on the surface of nonwoven fabrics (JP 01-249063 A, JP 03-502094 A, etc.). The surface is reformed with an objective of increasing the platelet permeation rate in JP 01-249063 A, whereas the surface is provided with hydrophilic properties easily to ensure priming with blood in JP 03-502094 A. Thus, neither of the prior art documents has an objective of increasing the adsorption probability of leukocytes, or leukocytes and platelets.
On the other hand, JP 06-247862 A discloses a filter material having basic functional groups and nonionic hydrophilic groups at a molar ratio of the basic functional groups to the nonionic hydrophilic groups of not less than 0.6 to less than 6 and having a content of the basic functional groups of not less than 5×10−5 meq/m2 to less than 0.1 meq/m2. However, this filter exhibits an insufficient effect of suppressing erythrocyte adhesion, and does not stably ensure the improvement of the leukocyte reduction performance.
WO 87/05812 discloses a filter element coated with an appropriate amount of a polymer having nonionic hydrophilic groups and basic nitrogen-containing functional groups and containing the basic nitrogen-containing functional groups in an amount of not less than 0.2 wt % to less than 4.0 wt %. An example showing superior leukocyte reducing capability and platelet permeability of the filter is presented. WO 87/05812 also presents a comparative example showing increased reduction of both platelets and leukocytes if a polymer containing more basic nitrogen-containing functional groups is used. WO 87/05812, however, concretely describes the treatment with respect to cattle blood only. No specific information about the treatment with respect to human blood is given. Performance of reducing leukocytes and platelets from human blood has not been known. In addition, WO 87/05812 does not disclose any information on the reduction of leukocytes and platelets from an erythrocyte preparation.
The inventors of the present invention have previously prepared a filter for blood processing by coating a filter substrate with a polymer and discovered that the content of low molecular weight components in the polymer relates to the leukocyte reduction rate in human whole blood processing. The inventors have filed an application for patent on a filter for reducing leukocytes from whole blood (Japanese Patent Application No. 2000-099715). However, the invention did not investigate simultaneous reduction of leukocytes and platelets from a whole blood preparation or an erythrocyte preparation.